Tobacco use is considered to be a preventable cause of major illness and death in the United States (U.S. Department of Health and Human Services (U.S. DHHS), January 2000, Healthy People 2010). During the past several decades, the public health community has repeatedly highlighted the health consequences of smoking cigarettes. Cardiovascular diseases, respiratory diseases and cancers that are attributable to smoking are extensive and growing, as evidenced by the most recent Surgeon General Report (The Health Consequences of Smoking, Surgeon General's Report, 2004). The Center for Disease Control has estimated that more than 440,000 premature deaths per year in the U.S. are attributable to cigarette smoking (Center for Disease Control, Targeting Tobacco Use, 2004).
While smoking rates in the developed world have leveled off over the last thirty years, and have even decreased in some countries, smoking rates and cigarette consumption rates in the developing world have increased during this same time period and will likely continue to do so for the foreseeable future. Current projections show that the number of smokers worldwide will increase from the present 1.3 billion to more than 1.7 billion in 2025 (due in part to an increase in global population) if the global prevalence of tobacco remains unchanged (World Health Organization, 2004).
Total cigarette consumption worldwide continues to increase. In terms of volume, total world consumption of cigarettes increased by 4 percent between 1995 and 1999, from 4.763 trillion cigarettes to 4.953 trillion cigarettes. The manufactured tobacco-products market is dominated by cigarettes, which account for 96 percent of global market value (The World Market for Tobacco Products, published by Euromonitor International, 2000 Edition, p. 2). In 2002, the worldwide market grew to 5.322 trillion cigarettes (Action on Smoking and Health, Factsheet No:18; January, 2004).
Considering the magnitude and growth rate of these numbers, it is clear that people will be smoking cigarettes for a long time to come. It is predicted that cigarette smoking could cause up to one billion premature deaths worldwide by the end of the 21st Century. Present statistics demonstrate that there is about one lung cancer death for every 3 million cigarettes consumed (Nature Cancer Reviews, October 2001).
The ideal solution to this health care dilemma is for all cigarette smokers to quit. However, such a solution appears unrealistic. Prohibitionist anti-tobacco policies from the anti-tobacco lobby have been unsuccessful for the most part given the increasing worldwide consumption of tobacco products. These policies in the Western world, where they are most prevalent, have hardly reduced smoking rates over the last twenty years. A significant percentage of cigarette smokers have no desire to quit smoking. Even though tens of millions of people in the U.S. alone have quit smoking, many before the advent of the many forms of nicotine replacement therapies (NRTs), a segment of smokers are not successful in their attempts to quit. An effective strategy for reducing the adverse effects of cigarette smoking for these two groups has been deficient.
A recent report issued by the Institute of Medicine (IOM) of the National Academy of Sciences, at the request of the U.S. Food and Drug Administration, has laid the foundation for a potential remedy to the current impasse. The resulting 656-page report titled Clearing the Smoke: Assessing The Science Base For Tobacco Harm Reduction (IOM Report), expresses an urgent public-health need for Potential Reduced-Exposure Products (“PREPs”), especially cigarettes (Institute of Medicine, Washington, D.C.: National Academy Press, 2001).
The first conclusion of the IOM Report is that: “For many diseases attributable to tobacco use, reducing risk of disease by reducing exposure to tobacco toxicants is feasible. This conclusion is based on studies demonstrating that for many diseases, reducing tobacco smoke exposure can result in decreased disease incidence with complete abstinence providing the greatest benefit.” (IOM Report Executive Summary, pg. 4).
PREPs are therefore a public-health policy necessity when considering all economic and political dynamics. The marketing and regulation of science-based PREPs needs to be included as part of any complete public-policy strategy on tobacco. The overall goal of reducing tobacco use, including reasonable tobacco marketing restrictions to adults, strict enforcement of sales and marketing to children, and education on the harmful effects of smoking, should go hand-in-hand with the availability of PREPs to consumers to reduce tobacco's overall toll on society.
Cigarette smoke is made up of two phases: a particulate phase, which is commonly called “tar” or total particulate matter; and a vapor phase, which contains gases and semi-volatile compounds. A common definition for “tar” is “nicotine-free dry smoke” or “nicotine-free dry particulate matter” (NFDPM). More specifically, “tar” is the total particulate matter isolated from smoke, excluding water and alkaloid compounds, including but not limited to nicotine. Approximately four-fifths of the weight of tobacco smoke is made up of ambient air, which includes carbon monoxide, carbon dioxide, water, hydrogen, methane, nitrogen and oxygen. The remaining one-fifth comprises the particulate phase and semi-volatile compounds. Tar makes up less than ten percent of the weight of cigarette smoke. Yet it is the tar component that contains the majority of the most harmful compounds.
Cigarette smoke is an extremely complex mixture of chemical compounds. Years of chemical analysis of cigarette smoke have demonstrated upwards of 6000 components (tar plus gases). Approximately 4800 compounds have been identified in the tar portion of cigarette smoke (Green and Rodgman, Recent Advances in Tobacco Science, 22:131-304, 1996). Analytical methods combined with sensitive biological assays have led to the identification of 69 carcinogens in tobacco smoke (The Changing Cigarette: Chemical Studies and Bioassays, Dietrich and Ilse Hoffman, Chapter 5, Smoking and Tobacco Control Monograph No. 13, NIH Pub. No. 02-5074, October 2001).
It has become clear to researchers, however, that not all components of cigarette smoke have equal toxicity. Notably, the first U.S. Surgeon General's report on smoking in 1964 came to the conclusion that nicotine was probably not toxic at the levels inhaled by smokers, with the implication that the source of the primary pharmacologic reward to smokers was not of immediate concern (Gori, p. 3, Virtually Safe Cigarettes—Reviving an Opportunity Once Tragically Rejected, 2000). In fact, the Surgeon General's report indicated, “There is no acceptable evidence that prolonged exposure to nicotine creates either dangerous functional changes of an objective nature or degenerative diseases” (U.S. Surgeon General Report 1964, pg. 74). Indeed, the U.S. Food and Drug Administration now allows the sale of nicotine patches and chewing gums as smoking cessation devices that may contain more nicotine than a pack of cigarettes.
“Alkaloids” are complex, nitrogen-containing compounds that naturally occur in plants, and have pharmacological effects in humans and animals. “Nicotine” is the primary natural alkaloid in commercialized cigarette tobacco and accounts for about 90 percent of the alkaloid content in Nicotiana tabacum. Other major alkaloids in tobacco include cotinine, nornicotine, myosmine, nicotyrine, anabasine and anatabine (J. C. Leffingwell, Chapter 8 Leaf Chemistry, Tobacco: Production, Chemistry and Technology, pg. 275, 1999). Minor tobacco alkaloids include nicotine-n-oxide, N-methyl anatabine, N-methyl anabasine, pseudooxynicotine, 2,3 dipyridyl and others (“Biosynthesis and Metabolism of the Tobacco Alkaloids”, Edward Leete in Alkaloids: Chemical and Biological Perspectives, Volume I, S. William Pelletier, Ed. 1983). Some of nicotine's common effects in humans are increased blood pressure and heart rate and improvements in concentration and short-term memory. Nicotine analogs and compounds are the subject of much recent research since they show promise in treating some diseases such as Alzheimer's and Parkinson's. Other tobacco alkaloids have similar but reduced activity compared to nicotine.
The most common measurements of cigarette smoke deliveries are reported as tar and nicotine. Tar and nicotine yields of cigarettes are shown in all consumer cigarette advertisements in the United States and numerous other countries. In many countries, yields (per cigarette) for tar, nicotine and even carbon monoxide are required to be printed on cigarette packaging. During the past several decades, cigarette design innovations have focused largely on tar and nicotine yield reductions, based on a belief embraced by the U.S. Surgeon General and the public health community that “less ought to be better” (See FIG. 1).
In the United States, tar, nicotine, and carbon monoxide yields are obtained using the Federal Trade Commission (FTC) smoking-machine test method, which defines the measurement of tar as that material captured by a Cambridge pad when a cigarette is machine smoked, minus nicotine and water (Pillsbury, et al., 1969, “Tar and nicotine in cigarette smoke”. J. Assoc. Off. Analytical Chem., 52, 458-62). Specifically, the FTC cigarette-testing method collects smoke samples by simulating puffing volumes of 35 ml of cigarette smoke for two seconds every 58 seconds, with none of the filter ventilation holes blocked (if any), until the burn line reaches the tipping paper plus 2 mm, or a line drawn 23 mm from the end of a non-filter cigarette. This FTC smoking-machine test method has been used in the United States since 1967 to determine smoke cigarette yields for tar and nicotine. The determination of carbon monoxide yields in cigarette smoke was added to this method in 1980.
In 1967, when the FTC introduced its testing method, it issued a news release and explained that the purpose of the testing “is not to determine the amount of tar and nicotine inhaled by any human smoker, but rather to determine the amount of tar and nicotine generated when a cigarette is smoked by a machine in accordance with the prescribed method.” Nevertheless, the method serves an important role in providing an accurate way to rank and compare cigarettes according to tar, nicotine and carbon monoxide yields.
The International Standards Organization (ISO) developed a very similar smoking-machine test method for tar, nicotine, and carbon monoxide yields of cigarettes (ISO, 1991 “Cigarettes—determination of total and nicotine-free dry particulate matter using a routine analytical smoking machine” ISO: 4387:1991).
The FTC and ISO smoking methods differ in the following eight areas.                The FTC method specifies laboratory environmental conditions of 75° F.±1° F. (23.8° C.±1° C.) and a relative humidity of 60%±2% for both the equilibration and testing. The time of equilibration is a minimum of 24 hours and a maximum of 14 days. This is compared to the ISO specifications of 22° C.±1° C. and 60%±2% relative humidity for equilibration, 22° C.±2° C. and 60% relative humidity±5% for testing. The equilibration time is a minimum of 48 hours and a maximum of 10 days.        The FTC defines the cigarette butt length as a minimum of 23 millimeters or the tipping paper plus three millimeters whichever is longer. ISO defines butt length as the longest of 23 millimeters or tipping paper plus three millimeters or the filter plus eight millimeters. Both methods specify a 23-millimeter butt length for non-filter cigarettes.        ISO defines the position of the ashtray at 20-60 millimeters below the cigarettes in the smoking machine. FTC does not specify a position.        ISO specifies a two-piece snap together reusable filter holder. This filter holder contains the Cambridge pad and uses a synthetic rubber perforated washer to partly obstruct the butt end of the cigarette. The FTC method defines the use of a Cambridge filter pad but does not specify a filter pad holder assembly.        The ISO method specifies airflow across the cigarettes at the cigarette level. FTC specifies the use of a monitor cigarette to adjust airflow.        The ISO procedure defines the process of wiping the excess total particulate matter (TPM) out of the used filter holder. The inner surfaces of the filter holder are wiped with two separate quarters of an unused conditioned filter pad. The FTC method uses the backside (the side opposite of the trapped TPM) to wipe the inner surface of the filter holder.        ISO specifies using 20 ml per Cambridge pad of extraction solution to analyze nicotine and water in TPM. The FTC procedure defines 10 ml per Cambridge pad.        ISO defines the internal standards for the gas chromatographic determination of nicotine and water. The FTC procedure does not specify the internal standards.        
These differences typically result in slightly lower measured deliveries for the ISO Method versus the FTC Method. The measured values between FTC and ISO methods are within the detection limits of the test or about no greater than 0.4 mg tar and about 0.04 mg nicotine for cigarettes that yield over about 10 mg.
The primary criticism of the FTC/ISO smoking-machine test methods (“FTC/ISO Method” or “FTC or ISO Method”) is that they do not accurately predict an individual smoker's level of exposure to tar, nicotine or carbon monoxide from smoking a particular cigarette National Cancer Institute Smoking and Tobacco Control Monograph 13, “Risks Associated with Smoking Cigarettes with Low Machine-measured Yields of Tar and Nicotine). These methods obtain test results under standardized conditions. However, an individual's smoking behavior may, and in most cases does, vary widely from how these standardized machines smoke cigarettes.
A human smoker may be exposed to extremely different levels of tar, nicotine and carbon monoxide per cigarette (for the exact same brand style of cigarettes) compared to the values derived from the FTC/ISO Method depending on various factors, including the smoker's frequency of puffs and volume of the inhalation of such puffs, duration of the smoke inhalation being held before exhaling, number of cigarettes smoked within a specified time period, and the percentage of the cigarette that is smoked (how far down the cigarette is smoked).
Two people that smoke the exact same cigarette brand style and the same number of daily cigarettes may not necessarily be exposed to the same levels of tar, nicotine, and carbon monoxide. Furthermore, an individual smoker is exposed to different per cigarette levels of tar, nicotine and carbon monoxide at different times. For instance, if a smoker is on a transatlantic flight and has not had a cigarette for 8 hours, he or she will most likely smoke the next cigarette very aggressively and be exposed to higher levels of tar, nicotine, and carbon monoxide than his or her per cigarette average. On the other hand, if a smoker has had many more cigarettes than usual over a brief time period, subsequent cigarettes may be smoked less aggressively, thereby exposing the smoker to less tar, nicotine, and carbon monoxide (on a per cigarette basis) than average for that smoker. Other factors, including stress, affect how often and how aggressively people smoke. Stress generally increases a smoker's nicotine consumption (IOM Report p. 254).
Filtered cigarettes can be designed to yield less tar, nicotine, and carbon monoxide according to the FTC/ISO Method. This can be accomplished by reducing the yields of these smoke fractions per puff. It is known that lower-tar, lower-nicotine and lower carbon monoxide cigarettes may be obtained by incorporating any one or more of the following modifications (“Cigarette Design”, Lynn T. Kozlowski, et al., NCI Monograph 13, Chapter 2, pg. 15):                Making the filter more efficient so that it filters out more of the smoke;        Using higher porosity cigarette paper;        Putting or increasing the number of ventilation holes (including increasing their size) around the filter-tipping material so that when the smoker draws on the cigarette more air comes into the smoke mixture, thereby diluting the amount of smoke inhaled;        Increasing the cigarette burn rate with chemical additives in the cigarette paper or filler;        Using a higher percentage of reconstituted sheet tobacco made from tobacco scraps including tobacco stems and dust;        Using expanded tobacco, which creates less tar and nicotine per cigarette since less mass of whole leaf tobacco fills the cigarette rod;        Reducing the diameter of the cigarette thus reducing the weight of the filler; and        Increasing tipping paper length which changes the butt length.FIG. 1 puts these methods in a historical perspective and shows the resulting decreases in tar and nicotine yields.        
“Reconstituted tobacco” (“recon”) is an important part of tobacco filler made from tobacco dust and other tobacco scrap material, processed into sheet form and cut into strips to resemble tobacco. In addition to the cost savings, reconstituted tobacco is very important for its contribution to cigarette taste from processing flavor development using reactions between ammonia and sugars.
“Expanded tobacco” is another important part of tobacco filler which is processed through expansion of suitable gases so that the tobacco is “puffed” resulting in reduced density and greater filling capacity. It reduces the weight of tobacco used in cigarettes. Advantageously, expanded tobacco reduces tar, nicotine and carbon monoxide deliveries and finds use, for example, in making low tar, low nicotine, and low carbon monoxide delivery cigarettes.
Nicotine content and, to a lesser extent, the tar level that cigarette smoke produces, also depends on the type and variety of tobacco used to produce the cigarette. The three types of tobaccos generally used in American brands of cigarettes are flue-cured, burley and oriental. Mixing these produces what has been referred to as “American blend” cigarettes. Generally, burley has the highest level of nicotine, followed by flue-cured and oriental. Most varieties of cured tobacco at fifteen percent moisture contain about one to three percent nicotine by weight. The alkaloid content in finished cigarettes is less than the amount in the freshly harvested tobacco leaf used to make cigarettes because losses occur during the curing, storing and manufacturing processes.
“Curing” is the aging process that reduces moisture and brings about the destruction of chlorophyll giving tobacco leaves a golden color and by which starch is converted to sugar. Cured tobacco therefore has a higher reducing sugar content and a lower starch content compared to harvested green leaf. “Flue-cured tobacco” refers to a method of drying tobacco plants in a ventilated barn with heat and is characterized by a unique color, high reducing sugar content, medium to heavy in body and exceptionally smooth smoking properties (Bacon, E. W., Wenger, R. & Bullock, J. F. (1952), Chemical changes in tobacco during flue-curing, Ind. Eng. Chem., 44, 292).
It is known that by varying the design of any of the components of the cigarette rod, as discussed above—for virtually all commercialized tobacco fillers—the levels of tar and nicotine that are measured by the FTC/ISO Method can be varied for a filtered cigarette from approximately 1 mg of tar and 0.05 mg of nicotine to approximately 20 mgs of tar and 1.8 mgs of nicotine.
When cigarettes are designed to be “lighter,” tar, nicotine, and carbon monoxide levels, as measured by the FTC/ISO Method, are reduced at slightly different rates. Nevertheless, the level of tar and carbon monoxide are not reduced by any sizable percentage without a corresponding reduction in the level of nicotine by approximately the same percentage and vice versa. Even though tar and nicotine yields per the FTC/ISO Method have been reduced over the last fifty years, the “tar-to-nicotine yield ratio” (“TNR”) of cigarettes has remained quite stable, as indicated in FIG. 1 and FIG. 2.
The term “cigarette” as used herein is defined as the “rod” plus, the “filler”. The cigarette “rod” includes the cigarette paper, filter, plug wrap (used to contain filtration materials), tipping paper that holds the cigarette paper (including the filler) to the filter, and all glues that hold these components together. The only components of the rod of a “non-filter cigarette” are the cigarette paper and glue that seals it. The “filler” includes (1) all tobaccos, including but not limited to reconstituted and expanded tobacco, (2) non-tobacco substitutes (including but not limited to herbs, non-tobacco plant materials and other spices that may accompany tobaccos rolled within the cigarette paper), (3) casings, (4) flavorings, and (5) all other additives (that are mixed into tobaccos and substitutes and rolled into the cigarette). The term “cigarette” as used herein is also defined as (A) any roll of tobacco wrapped in paper or any other substance not containing tobacco, and (B) any roll of tobacco wrapped in any substance containing tobacco which, because of its appearance, the type of tobacco used in the filler, or its packaging and labeling, is likely to be offered to, or purchased by, consumers as a cigarette described in subparagraph (A) (1967 Federal Cigarette Labeling And Advertising Act, U.S. FTC).
The terms “non-filter rod,” “full-flavor rod,” “light rod” and “ultra-light rod” as used herein are defined as a non-filter cigarette minus its filler, a full-flavor cigarette minus its filler, a light cigarette minus its filler, and an ultra-light cigarette minus its filler, respectively.
As used herein, the “tar-to-nicotine yield ratio” or “TNR” of a cigarette is calculated by dividing the tar yield by the nicotine yield, both of such yields being measured by the FTC or ISO Method.
Cigarette brands in the United States and throughout most of the world are differentiated by categories such as full-flavor, lights, and ultra-lights. These designations usually appear on cigarette packs and advertising. Such categories convey cigarette strength, which is a function of the level of tar and nicotine measured by the FTC or ISO Method. Stronger-tasting or full-flavor cigarettes have higher tar and nicotine yields. The categories or “strength” of cigarettes that are generally recognized in the United States as per the FTC Method are the following:                “full-flavor cigarette” (15 mg or more tar per cigarette)        “light cigarette” (7 to 14 mg tar per cigarette)        “ultra-light cigarette” (6 mg or less tar per cigarette).        
Consumer decisions on whether to smoke full-flavor versus light cigarettes based solely on tar and nicotine levels derived from the FTC/ISO Method are problematic (“Public Understanding of Risk and Reasons for Smoking Low-Yield Products”, Neil Weinstein, NCI Monograph 13, Chapter 6). Since humans and smoking machines smoke cigarettes differently, the consumer may have high expectations for a cigarette reported to have low-tar (“Consumer Perception of Cigarette Yields: Is the Message Relevant?”, Gio Gori, Regulatory Toxicology and Pharmacology volume 12, 64-68 1990). The smoker should not mistakenly believe that switching from full-flavor cigarettes (Marlboro® full-flavor produce 15 mg tar and 1.1 mg nicotine) to light cigarettes (Marlboro® lights yield 11 mg tar and 0.8 mg nicotine) will necessarily reduce the risks associated with smoking.
When light cigarette smokers are compared to full-flavor cigarette smokers (and ultra-light smokers compared to light smokers and ultra-light smokers compared to full-flavor smokers), and/or when an individual smoker who usually smokes full-flavor or light cigarettes switches to reduced yield cigarettes, or occasionally smokes reduced yield cigarettes, some or all of the following smoking behaviors may occur to some extent:                More puffs taken per cigarette;        Larger individual puffs or puff volume (e.g., 55 ml of smoke may be consumed versus 35 ml);        Variation in the duration of individual puffs (e.g., 4 seconds versus 2 seconds), therefore producing hotter cone temperatures, which have been associated with increased smoke mutagenicity*;        Holding smoke in the lungs for a longer duration before exhaling;        Deeper inhalation into the lungs;        Light cigarette smokers may block filter vent holes with fingers and lips; and        Smoking more cigarettes over a given period of time *(“Effect of pyrolysis temperature on the mutagenicity of tobacco smoke condensate”, White, J. L., et al., Food and Chemical Toxicology 39, pg. 499-505 (2001)). As stated in the IOM Report: “In order to maintain the desired intake of nicotine, many smokers who changed to low-yield products also changed the way they smoked in the manner previously described. Thus, their exposure to tobacco toxicants is higher than would have been predicted by standardized assays and people who have continued to use these products have not significantly reduced their disease risk by switching to them” (IOM Report p. 2).        
Differences in smoking behavior observed among smokers of full-flavor, light, and ultra-light cigarettes have been collectively called “compensation” (“Compensatory Smoking of Low Yield Cigarettes”, Neal Benowitz, NCI Monograph 13). “Compensation” is smoking more intensively due to the reduced presence of nicotine in tobacco smoke. Smokers compensate by smoking lower-yield cigarettes (versus higher-yield cigarettes) more aggressively in order to obtain their desired nicotine impact and mouth feel of smoke, which are important sensory properties (Jed E. Rose, “The role of upper airway stimulation in smoking,” Nicotine Replacement: A Critical Evaluation, p 95-106, 1988).
The Wilcox group has concluded that smokers who switch to lower-tar and nicotine cigarettes compensated by increasing their cigarette consumption per day compared to a control group. Data pooled from four cohorts failed to show a statistically significant benefit for low-tar cigarettes in terms of lung cancer risk, even among different levels of smoking (Tang et al., 1995b), as did another large cohort study (Sidney et al., 1993). Lee and Garfinkel provided a summary of lung cancer risk and type of cigarette smoked (Lee and Garfinkel, 1981) and were unable to demonstrate a significant decrease in risk based on tar content (IOM Report p. 401). Recent increases of adenocarcinomas in lower airways of smokers are hypothesized to be due to so-called smoking compensation of low-yield products. Smokers of these products inhale more deeply to increase their nicotine dose (IOM Report p. 285).
Consequently, the three-decade consumer trend towards “lighter” cigarettes may not have been beneficial to smokers' health. Generally, by compensation, smokers of light cigarettes inhale just as much tar and nicotine as full-flavor smokers. Of course, light cigarettes do taste differently than full-flavor cigarettes and these taste differences are usually why most smokers choose the brands styles that they do. However, in the U.S. alone, there are currently millions of smokers of light and ultra-light cigarettes that have switched from higher yielding cigarettes.
FIG. 2 shows tar and nicotine yields from the FTC Method for some American brand styles. “Brand style(s)” are different versions or styles of cigarettes within a brand family (e.g., Marlboro® ultra-lights kings filter box). FIG. 2 also shows the resulting TNRs of such brand styles. Whether the brand styles are king size (usually 85 mm in length), 100's (100 mm in length), full-flavor, lights, or ultra-lights, their resulting TNRs are relatively close in value. Ultra-lights tend to have somewhat lower TNRs, mainly due to the fact that the extra ventilation in the design of such cigarettes lowers yields (from the FTC/ISO Method) of tar at a slightly higher rate than nicotine. The simple average TNR of FIG. 2 is 14.22.
The sales weighted average of tar and nicotine yields for the 1998 FTC report was 12.0 mg tar and 0.88 mg nicotine, which gives a TNR of 13.64. FIG. 1 demonstrates that in 1950 the average TNR was about 14.44 (about 39 mg tar/about 2.7 mg nicotine). These numbers demonstrate that the average TNRs of American cigarettes from about 1950 to the present have been fairly consistent.
The 1998 FTC Report was released in 2000, covering the cigarette brands of 1998, and was the last year that the FTC chose to publicly release tar, nicotine and carbon monoxide yields from cigarettes. Out of the 1294 cigarette brand styles evaluated, only 3 have a calculated TNR below 8. In fact, only a total of 8 brand styles have calculated TNRs of less than 10. These consist of 1 Rothmans®, 3 Canadian Players®, 2 Old Gold®, 1 Now®, and 1 Carlton®. While only the tar, nicotine and carbon monoxide numbers were listed in the report, TNRs can be easily calculated from these numbers by dividing the yield of tar by the yield of nicotine. Two other Carlton® brand styles have yields of <0.5 tar and 0.1 nicotine. Since the actual raw numbers of the tar yields can not be determined and since there is an enormous impact due to rounding at these levels, the numbers for these 2 brand styles do not appear to reflect the prior art.
2 of the 3 brand styles with TNR's of less than 8 (Carlton® 100 filter soft pack and Now® king filter soft pack) were reported in the 1998 FTC Report to yield 1 mg tar and 0.2 mg nicotine, thereby having a TNR of 5. However, the TNRs of these 2 brand styles are mainly due to the nature of rounding small numbers. From the 1998 FTC report, “Tar and carbon monoxide ratings are rounded to the nearest milligram (mg.); those with 0.5 mg or greater are rounded up, while those with 0.4 mg or less are rounded down. The nicotine figures are rounded to the nearest tenth of a milligram. Those with 0.05 mg or greater are rounded up; those with 0.04 mg or less are rounded down.” Therefore, an ultra-light cigarette delivering 1.4 mg of tar and 0.15 mg nicotine would be reported as 1 mg tar and 0.2 mg nicotine (TNR of 5), even though the actual TNR would equal 9.33. Cigarettes delivering 1 mg of tar and 0.1 mg nicotine have low consumer acceptability due to smoke thinness (lack of taste) and too much draw resistance. In 2000, the market share of cigarette brand styles that yielded 1-3 mg tar pursuant to the FTC Method had a U.S. market share of only 1.3 percent. Ninety-two percent of the brand styles yielding 3 mg tar or less tar printed their FTC tar and nicotine ratings on their packs. This contrasts to brand styles that yielded 12 or more mg tar, in which only 0.01 of one percent printed their FTC tar and nicotine rating on their packs (FTC Cigarette Report for 2000, 2002, p. 15).
Further evidence that the FTC's rounding procedure is responsible for these 2 brand styles' TNRs of 5 in the 1998 FTC Report and do not appear to accurately reflect prior art is that the hard pack version of the Carlton® 100 filter soft pack brand style lists a rating of 1 mg tar and 0.1 mg nicotine (TNR of 10). It can be inferred that the “0.2” mg nicotine rounded number for the soft pack version was in reality close to 0.15 mg nicotine-in raw number terms. Similarly, the menthol version of the Now® king filter soft pack has a listed rating of 1 mg tar and 0.1 nicotine, which also means that the “0.2” nicotine rounded number for the non-menthol version was most likely close to 0.15 mg nicotine-in raw number terms. Also, the exact Carlton® (100 filter soft pack) brand style that is listed in the 2000, 2001, and 2002 FTC reports yields 1 mg tar and 0.1 mg nicotine (TNR of 10), not the 1 mg tar and 0.2 mg nicotine (TNR of 5) as listed in the 1998 FTC report.
10 out of the 12 brand styles (out of the 1294 total) that yield 1 mg tar also yield 0.1 mg nicotine (TNR of 10). The other 2 have been discussed above (Carlton® 100 filter soft pack and Now® king filter soft pack). The FTC's rounding procedure on the tar side may, and most likely does, contribute to reduce the TNRs of these 2 very low-yielding brand styles. It is likely that manufacturers target the yields of these 1 mg tar brand styles at about 1.4 mg tar and 0.14 mg nicotine, which is a balance of being able to advertise the 1 mg tar level on the brand's packaging and the negative taste considerations of having the cigarettes actually yield (without rounding) 1 mg tar or lower. This is most likely why extremely similar brand styles (hard pack as opposed to soft pack and menthol as opposed to non-menthol) go one way or another (having a TNR of 5 versus 10) due to rounding. Thus, these 2 brand styles do not appear to reflect the prior art.
The third brand style that has a TNR of lower than 8 in the 1998 FTC report was Old Gold® non-filter hard pack, which has a TNR of 5.55 (10 mg tar and 1.8 mg nicotine). This listing for a non-filter brand style appears erroneous. There are 72 non-filter brand styles listed in the 1998 FTC report. The lowest TNRs of these, after the Old Gold® non-filter hard pack, is English Ovals® non-filter, hard pack, which has a TNR of 13 (26 mg tar and 2.0 mg nicotine). In fact, the lowest tar yield of the non-filter group of 72, besides the Old Gold® non-filter hard pack, is Picayune® regular, non-filter soft pack full-flavor. This brand style's yield is 18 mg tar and 1.2 mg nicotine (a TNR of 15).
Due to a freedom of information request to the FTC, in October, 2003 the FTC released similar reports for the years 1999-2002. The Old Gold® non-filter hard pack brand style was not included in any one of the FTC's reports for these four years or in the 1997 FTC Report. The only Old Gold® non-filter brand style that is listed in these 5 FTC Reports (1997, 1999, 2000, 2001 and 2002) is Old Gold® non-filter soft pack, which yields 25 mg tar and 1.8 mg nicotine (TNR of 13.8) in 1997, 26 mg tar and 1.9 mg nicotine (TNR of 13.68) in 1999, 27 mg tar and 1.9 mg nicotine (TNR of 14.2) in 2000, 27 mg tar and 2.0 mg nicotine (TNR of 13.5) in 2001. There is no reason for the soft pack non-filter brand style to yield substantially (or even negligible) different levels of tar than a hard pack brand style. No Old Gold® brand styles were listed in 2002 FTC Report.
For the 2002 FTC Report, only the following 4 brand styles, out of 1250, have calculated TNRs of less than 8:                Merit® king filter ultima: 1 mg tar, 0.2 nicotine (TNR of 5);        Now® king filter menthol soft pack, ultra-light: 1 mg tar, 0.2 nicotine (TNR of 5);        Now® king filter soft pack, ultra-light: 1 mg tar, 0.2 nicotine (TNR of 5);        Now® 100 filter soft pack, ultra-light: 2 mg tar, 0.3 nicotine (TNR of 6.66).        
There is also another exact same brand style listed as Merit king filter ultima, yet this one yields 1 mg tar and 0.1 mg nicotine (TNR of 10). It is believed that the low TNRs of these brand styles are such for the same reasons as listed in the 1998 FTC report, and do not appear to accurately reflect the prior art. Only a total of 5 brand styles (out of 1250) have calculated TNRs of greater than 8 and less than 10 in the 2002 FTC report. These consist of 3 Canadian Players®, 1 Carlton®, and 1 other Merit®.
The recent trend in cigarette PREPs is reducing selected carcinogens in tobacco smoke. Two cigarette PREPs that have recently been introduced in the United States: Advance®, manufactured by Brown & Williamson Tobacco Company, and Omni®, manufactured by Vector Tobacco, Inc. Advance® achieves reductions of tobacco-specific nitrosamines (TSNAs) with patented (See U.S. Pat. Nos. 5,803,081, 5,845,647, 6,135,121, 6,202,649, 6,311,695, 6,338,348, 6,350,479, 6,425,401, RE38,123, and 6,569,470) and patent-pending (See U.S. Publication Nos. 20020174874 and 20030018997) tobacco leaf curing technologies in conjunction with specialized filtration technology.
Omni® reduces polycyclic aromatic hydrocarbons (PAHs), TSNAs, and catechols by using a palladium catalytic system (See U.S. Publication No. 20030000538) added to the filler and activated charcoal filtration. Omni®, king size full-flavor has 15 mg tar and 1.0 mg of nicotine (TNR of 15). Advance® lights king box has 10 mg tar and 0.8 mg of nicotine (TNR of 12.5).
A major dilemma in designing a PREP is that years of clinical studies may be required to understand the reduced risks, if any, of a PREP compared to conventional cigarettes. This is especially true of PREPs, similar to Advanced and Omni® that do not reduce whole tobacco smoke deliveries but only reduce some chemical compounds in tobacco smoke.
Polycyclic aromatic hydrocarbons (PAHs) are the result of the incomplete combustion of lipids and terpenes found naturally in tobacco. The scientific community considers these compounds to be potent carcinogens in tobacco smoke. Tobacco-specific nitrosamines are formed during the tobacco curing process and during smoking (Hoffman, D., Dong, M., & Hecht, S. S. (1977), Origin in tobacco smoke of N-nitrosonornicotine, a tobacco-specific carcinogen. Brief communication, J. Natl. Cancer Inst., 58, 1841-4). These are also considered potent carcinogens. TSNAs are formed by a reaction between a nitrosating agent and alkaloids found naturally in tobacco and are also carcinogens in tobacco smoke. (U.S. Publication No. 20040144397).
Even with reductions in these potent carcinogens, many other carcinogens in tobacco smoke are still present, which these technologies do not address. Also, many other compounds that may not cause cancer but are detrimental to other aspects of human health, such as cardiovascular and respiratory diseases, are not reduced.
Eclipse® and Accord® provide a smoking experience as close as possible to smoking a conventional cigarette but with minimal or no combustion (pyrolysis) of the tobacco. The intended advantage of these products is a significant reduction in the formation of compounds resulting from the combustion of tobacco in conventional cigarettes. These compounds are generally accepted as harmful to smokers. Since these two brands do not smoke like conventional cigarettes, they have not been very accepted by the market.
The smoking experience in both of these products relies on the following concepts. The smoke aerosol in both products is formed by heating tobacco materials containing a high content of glycerin rather than combusting the tobacco. Glycerin when heated, rapidly vaporizes, forming an inhaleable aerosol very similar in appearance and feel to cigarette smoke. Further, the heating of the tobacco materials contained in these products will release volatile flavors indigenous to the tobacco as well as nicotine. Any added tobacco volatile flavorings could be released into the smoke aerosol as well.
Eclipse® and Accord® use different methods of applying heat to the tobacco materials contained in their respective products. Accord® relies on a device known as a lighter that contains batteries, circuitry and heaters that will apply heat to a cigarette inserted into the device. It is designed in such a fashion as to deliver six puffs per cigarette inserted into the device. Cigarettes specifically manufactured for this device must be used for proper performance.
Eclipse® relies a combustible carbon tip that, when ignited, provides a source of heat to form a smoke aerosol from the tobacco materials contained in the product. The Eclipse® product has a appearance similar to a conventional cigarette, except that it is not consumed to ashes as compared to a conventional cigarette.
Both of these products pose challenges when attempting to determine the tar and nicotine delivery via the FTC method. The butt length determination is meaningless as neither product is consumed as it is puffed. The number of puffs on each product is limited by nature of their design. With Eclipse® the number of puffs is regulated by the carbon heat source. Accord® is electronically limited to six puffs. Finally, Accord® is not “lit” as prescribed by the FTC method.
It is known that Nicotiana rustica, which is high in nicotine content without being genetically modified, can be crossed with Nicotiana tabacum to produce a new plant (Wemsman, E. A., et al., Principles of Cultivar Development, Volume 2, Crop, Species, Ed. W. R. Fehr, Macmillan, New York 1987). Y-1 tobacco, which was initially and partially developed by the U.S. Department of Agriculture, is an example of this crossing. However, such a variety takes many more years to create than increased-nicotine tobacco by transgenic means. Other advantages of creating increased-nicotine tobacco by transgenic means versus plant crossing techniques is that transgenic processes can be performed on any type of commercialized tobacco (flue-cured, burley, and oriental) or cultivar (or variety) of tobacco, thereby maintaining the vast majority of the traits of the parent tobacco line before the genetic modification. Desirable commercial characteristics of a N. tabacum variety will be negatively affected when it is crossed with N. rustica. 
FIG. 3 demonstrates that only 36.4 percent of all smoking-related deaths in the U.S. are caused by cancer, yet the public's perception is that cancer is the greatest detrimental health effect of smoking. In fact, cardiovascular diseases cause 42.4 percent and respiratory diseases cause 21.2 percent of such deaths. Epidemiological studies show a substantial drop in risk as the total amount of inhaled smoke decreases (U.S. Surgeon General, 1964, 1979, 1989). Since it is not know which of many toxins cause specific harmful effects, it would be beneficial to reduce whole tobacco smoke deliveries to the smoker to create an effective PREP—not just a handful of smoke constituents that are carcinogens.
The IOM report concludes that “Nicotine is one of the factors crucial to the success of a tobacco product.” (p. 29). Accordingly, retaining nicotine at pleasurable levels, while reducing the more toxic components of tobacco, would be another general strategy for harm reduction (IOM Report p. 29). By reducing the dose of whole tobacco smoke that is inhaled per cigarette and/or reducing the number of cigarettes smoked per day, all carcinogens and harmful gases would be reduced by similar percentages. The most effective way to accomplish reductions in whole tobacco smoke deliveries, given a smoker's propensity to compensate, is to reduce the TNR of cigarettes. With reduced TNR cigarettes, the per-puff level of whole tobacco smoke that the smoker inhales, which includes tar and carbon monoxide, would be reduced in many cases while maintaining the smoker's required nicotine level.
According to epidemiologic evidence, risk relates linearly to the amount of cigarettes smoked. The evidence of reduced dose should be the foundation of less hazardous cigarette regulation (Gori, 2002 Coresta Congress). A “dose-response relationship” is defined as the relationship between disease-risk regression and exposure regression (e.g., the higher the dose, the greater incidence of disease). “Currently available data allow estimation, albeit imprecise, of a dose response relationship between exposure to whole tobacco smoke and major diseases that can be monitored for evaluation of harm reduction potential” (p. 9, IOM Report). Since a dose-response relationship currently exists for whole tobacco smoke, the benefits of low TNR cigarettes which can reduce whole tobacco smoke deliveries to smokers could be promptly evaluated and endorsed by public health regulators such as the U.S. Food and Drug Administration (FDA).
In FIG. 2, if the tar yield from the FTC Method for Marlboro® full-flavor kings of 15 mg is compared with the tar yield from the FTC Method for Marlboro® lights kings of 11 mg, then a 4 mg reduction of tar is observed. This might, on the surface, indicate that a smoker would inhale 4 mg less tar by switching to the light product. However, the TNR values of 13.64 and 13.75 respectively, show no improvement in switching in terms of the amount of tar inhaled per mg of nicotine per cigarette. Since compensation may occur when switching from full-flavor to light or ultra-light cigarettes and from light to ultra-light cigarettes, TNR values may provide a more accurate representation of a cigarette brand's true smoke delivery with respect to human smoking behavior.
It is well known that the motivations of smokers extend to a variety of factors such as taste, esthetic, and behavioral incentives, of which the pharmacologic rewards of nicotine are by far the most significant. With the exception of extremely low yield cigarettes, smokers in general manage to utilize an average of about 1 mg of nicotine (per cigarette) from cigarettes of any brand, regardless of the machine yields on the standard FTC smoking machine (Gori, pg. 3 Virtually Safe Cigarettes—Reviving an Opportunity Once Tragically Rejected, 2000). “The ceiling of how much nicotine a smoker inhales is about 2 mg per cigarette. The number of puffs per cigarette averages around eight. Thus a top delivery of 250 micrograms per puff would be enough to satisfy peak demands, although usually smokers will extract and inhale less than this maximum delivery” (Gori, Gio, Less Hazardous Cigarettes, Tobacco Reporter, p. 31, June, 2004).
In a British Medical Journal article (BMJ, 1976 volume 1, pp. 1430-1433) and again in a 1980 Banbury Report (#3 A Safe Cigarette, pp. 297-310), Michael Russell advocated low-tar, medium-nicotine and low-carbon monoxide cigarettes as safer alternatives to cigarettes available on the market at that time. A review of German tobacco industry research from Internet documents indicated that scientists thought a safer cigarette would have a greater ratio of nicotine to tar (lower TNR) (Tobacco Control 2000; 9:242-248, pg. 4).
A desirable reduced-exposure cigarette should deliver a smoker's desired level of nicotine per cigarette as cleanly and efficiently as possible while maintaining acceptable taste. In fact, “reverse compensation” may occur in a number of situations with low TNR cigarettes, since smokers inhale less whole tobacco smoke while obtaining a satisfactory amount of nicotine. “Reverse compensation” is defined as smoking less intensively due to the increased presence of nicotine in tobacco smoke.
Low TNR cigarettes would also benefit nonsmokers. By more efficiently delivering nicotine to smokers, less cigarettes per day may be smoked and less of each cigarette may be smoked, which will generate less sidestream smoke (what arises from the lit end of a cigarette, mostly between puffs) and less environmental tobacco smoke (smoke present in air, consisting of exhaled mainstream smoke and sidestream smoke). Mainstream smoke (mainstream whole tobacco smoke) is what emerges from the (smoker's) “mouth” or butt end (filter tip) of a puffed cigarette (IOM Report p. 283).
Accordingly, there is a need for low TNR cigarettes that can more efficiently deliver the physiological effect of nicotine without as much harmful tar and gases.